Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
  • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
  • C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
  • C07D451/06—Oxygen atoms
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
• • C—CHEMISTRY; METALLURGY
  • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
  • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
  • C09B11/00—Diaryl- or thriarylmethane dyes
  • C09B11/04—Diaryl- or thriarylmethane dyes derived from triarylmethanes, i.e. central C-atom is substituted by amino, cyano, alkyl
  • C09B11/10—Amino derivatives of triarylmethanes
  • C09B11/12—Amino derivatives of triarylmethanes without any OH group bound to an aryl nucleus
  • C09B11/18—Preparation by oxidation

Definitions

• This invention relates to a new derivative of dibenzocyclo-heptane, to processes for its preparation, and to pharmaceutical preparations containing it. It is an improvement of the invention described and claimed in the specification of my copending US. application Serial No. 16,660 filed March 22, 1960, now Patent No. 3,119,829.
• the compounds of Formula I are useful as antihistaminics and, moreover, have a very strong anti-acetylcholine activity.
• the present invention accordingly provides the hitherto unknown compound 3-(dibenzo[a,d]-1,4-cyclohepta dien--yloxy)nortropane of the planar formula:
• the compound of Formula II possesses pharmacological properties which are useful in therapeutic applications; in particular, it exerts a strong atropine-like action, decreasing locomotor activity.
• the compound may, moreover, be utilized as an intermediate in the production of other therapeutically active compounds, wherein the hydrogen atom on the nitrogen atom of the nortropane nucleus is replaced by groups such as an alkyl radical.
• the compound of Formula II may be prepared by reacting nortropine with a dibenzo(a,d) 1,4 cyclo- 2 heptadien-S-yl halide.
• the etherification reaction is preferably carried out by heating the reactants in an inert,
• anhydrous organic solvent such as benzene, toluene or xylene, advantageously containing a tertiary amine (preferably a tri(lower)alkylamine, e.g. tributylamine) or other suitable acid-binding substance.
• a modification of this method comprises reacting dibenzo(a,d)-1,4-cycloheptadien-5-yl halide with an alkali metal salt such'as the sodium or potassium salt of nortropine.
• the compound of Formula II may also be prepared by de-methylating 3-(dibenzo[a,d]-1,4-cycloheptadien-5 yloxy)tropane by methods known per se for the demethylation of methylamino compounds.
• the de-methylation may be effected, for example, by replacement of the methyl group with a cyano group through treatment of the tropane derivative with a cyanogen halide (preferably cyanogen bromide), then hydrolysis of the resultant N- cyano nortropane compound followed by decarboxylation of the N-carboxy nortropane compound thus formed.
• a cyanogen halide preferably cyanogen bromide
• Acid addition salts of 3-(dibenzo[a,d]-1,4-cycloheptadien-S-yloxy)nortropane may be obtained in manner known per se.
• the salts are obtainable by treatment of the base in an appropriate solvent medium, e.g. diethyl ether, with an equivalent quantity of an acid.
• the compound of the invention when used for therapeutic purposes may be employed as such or in the form of a non-toxic acid addition salt, i.e. a salt which is not harmful to the animal organism when used in therapeutic doses, derived from an inorganic acid, such as the hydrohalic acids (e.-g. hydrochloric and hydrobromic acids), or an organic acid such as oxalic, maleic, fumaric, citric and tartaric acids.
• a non-toxic acid addition salt i.e. a salt which is not harmful to the animal organism when used in therapeutic doses
• an inorganic acid such as the hydrohalic acids (e.-g. hydrochloric and hydrobromic acids), or an organic acid such as oxalic, maleic, fumaric, citric and tartaric acids.
• EXAMPLE I A mixture of 6 g. of nortropine, 23.6 g. of dibenzo (a,d)-1,4-cycloheptadien-5-yl' chloride and 8.9 g. of tributylamine, dissolved in 175 ml. of anhydrous toluene is heated under reflux for a period of 6 hours.
• the mix- EXAMPLE II (a) Preparation of-3-(dibenzo[a,d]-1,4-cycl0- heptadien-S-yloxy tropano nitrile To 11.66 g. of cyanogen bromide in ml. of henzene, a solution of 33.0 g.
• the invention includes within its scope pharmaceutical preparations containing 3-dibenzo[a,d]-1,4-cycloheptadien-S-yloxy)nortropane, or non-toxic acid addition salt thereof, in association with a pharmacologically acceptable carrier.
• the preparation may take any of the forms customarily employed for administration of therapeutically active substances, but the preferred types are those suitable for oral administration and especially tablets, pills, and capsules, including the substance.
• the tablets and pills may be formulated in manner known per se with one or more pharmacologically acceptable diluents or excipients, such as lactose or starch, and include materials of a lubricating nature such as magnesium or calcium stearate, and colouring substances.
• Capsules made of absorbable material may contain the active substance alone or in admixture with a solid or liquid diluent.
• Liquid preparations may be in the form of suspensions, emulsions, syrups or elixirs of the active substance in water or other liquid medium commonly used for making orally acceptable pharmaceutical formulations, such as liquid paraffin, or a syrup or elixir base.
• the active substance may also be made up in a form suitable for parenteral administration, i.e. as a suspension or emulsion in sterile water or an organic liquid usually employed for injectable preparations, for example a vegetable oil, such as olive oil or a sterile solution in an organic solvent.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (1)

Publications (1)

Family

ID=9812846

Family Applications (1)

Country Status (9)

Cited By (4)

Families Citing this family (2)

Citations (1)

Family Cites Families (2)

• 0
  • BE BE637978D patent/BE637978A/xx unknown
• 1963
  • 1963-02-15 GB GB6348/63A patent/GB988291A/en not_active Expired
• 1964
  • 1964-02-12 US US344243A patent/US3351625A/en not_active Expired - Lifetime
  • 1964-02-13 NL NL6401268A patent/NL6401268A/xx unknown
  • 1964-02-14 DK DK9065AA patent/DK106556C/da active
  • 1964-02-14 SE SE1809/64A patent/SE318888B/xx unknown
  • 1964-02-14 BE BE643795D patent/BE643795A/xx unknown
  • 1964-02-14 CH CH176364A patent/CH437302A/de unknown
  • 1964-02-14 DK DK72664AA patent/DK105593C/da active
  • 1964-02-15 DE DEN24452A patent/DE1289849B/de active Pending
  • 1964-02-15 FR FR963926A patent/FR4155M/fr not_active Expired

Patent Citations (1)

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